The use of modified antisense oligonucleotides as potential chemotherapeutics is currently progressing from in vitro studies in research labs to pharmacology studies using animal models. As yet, there exists no commercial DNA synthesizer capable of producing a variety of modified oligonucleotides on a large scale. The proposed research is designed to develop a commercial DNA synthesizer, optimized for H- phosphonate chemistry, capable of producing multigram quantities of modified oligonucleotides will be prepared. Also, techniques will be designed for the purification of these products on a pharmaceutical scale.